2-Decarboxy-2-alkylcarbonyl-PGD compounds

ABSTRACT

The present invention provides novel prostaglandin analogs wherein the C-2 carboxyl is replaced by alkylcarbonyl, i.e., a C-2 ketone. These novel 2-decarboxy-2-alkylcarbonyl-PG-type compounds are disclosed as improved gastrointestinal cytoprotective agents, being devoid or substantially devoid of other prostaglandin-type effects (e.g., smooth muscle or cardiovascular).

The present application is a divisional application of Ser. No. 888,695, filed Mar. 21, 1978, now U.S. Pat. No. 4,123,463.

The present invention relates to prostaglandin analogs, for which the essential material constituting disclosure therefor is incorporated by reference here from U.S. Pat. No. 4,123,463. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## wherein D is ##STR2## wherein R₁ is alkyl of one to 4 carbon atoms, inclusive; WHEREIN L₁ is ##STR3## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is methyl only when the other is hydrogen or methyl;Wherein M₁ is ##STR4## wherein R₅ is hydrogen or methyl; WHEREIN R₇ is (1) --(CH₂)_(m) --CH₃, ##STR5## WHEREIN H IS ZERO TO THREE, INCLUSIVE, WHEREIN M IS ONE TO 5, INCLUSIVE, S IS ZERO, ONE, 2, OR 3 AND T is chloro, fluoro, trifuloromethyl, alkyl of one to 3 carbon atoms or alkoxy of one to 3 carbon atoms, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl;Wherein Y₁ is (1) trans--CH═CH--, (2) cis--CH═CH--, (3) --ch₂ ch₂ --, or (4) --C.tbd.C--; andWherein Z₁ is (1) cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --, (2) cis--CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, (3) cis--CH₂ --CH═CH--(CH₂)_(g) --CH₂ --, (4) --(ch₂)₃ --(ch₂)_(g) --CH₂ --, (5) --(ch₂)₃ --(ch₂)_(g) --CF₂ --, (6) --ch₂ --o--ch₂ --(ch₂)_(g) --CH₂ --, (7) --(ch₂)₂ --o--(ch₂)_(g) --CH₂ --, (8) --(ch₂)₃ --o--(ch₂)_(g) --, (9) --C.tbd.C--CH₂ --(CH₂)_(g) --CH₂ --, (10) --ch₂ --c.tbd.c--(ch₂)_(g) --CH₂ --, or (11) trans--(CH₂)₂ --(CH₂)_(g) --CH═CH--,wherein g is one, two, or three.
 2. A prostaglandin analog according to claim 1, wherein R₁ is methyl.
 3. A prostaglandin analog according to claim 2, wherein D is ##STR6##
 4. 2-Decarboxy-2-methylcarbonyl-8β,12α-PGD₂, a prostaglandin analog according to claim
 3. 5. A prostaglandin analog according to claim 2, wherein D is ##STR7##
 6. 2-Decarboxy-2-methylcarbonyl-9β,PGD₂, a prostaglandin analog according to claim
 5. 7. A prostaglandin analog according to claim 2, wherein D is ##STR8##
 8. 2-Decarboxy-2-methylcarbonyl-8β,9β,12α-PGD₂, a prostaglandin analog according to claim
 7. 9. A prostaglandin analog according to claim 2, wherein D is ##STR9##
 10. A prostaglandin analog according to claim 9, wherein Y₁ is cis--CH═CH--.
 11. 2-Decarboxy-2-methylcarbonyl-13-cis-PGD₁, a prostaglandin analog according to claim
 10. 12. A prostaglandin analog according to claim 9, wherein Y₁ is --CH₂ CH₂ --.
 13. 2-Decarboxy-2-methylcarbonyl-13,14-dihydro-PGD₁, a prostaglandin analog according to claim
 12. 14. A prostaglandin analog according to claim 9, wherein Y₁ is --C.tbd.C--.
 15. 2-Decarboxy-2-methylcarbonyl-13,14-didehydro-PGD₁, a prostaglandin analog according to claim
 14. 16. A prostaglandin analog according to claim 9, wherein Y₁ is trans--CH═CH--.
 17. A prostaglandin analog according to claim 16, wherein R₇ is ##STR10##
 18. 2-Decarboxy-2-methylcarbonyl-17-phenyl-18,19,20-trinor-PGD₁, a prostaglandin analog according to claim
 17. 19. A prostaglandin analog according to claim 16, wherein R₇ is ##STR11##
 20. 2-Decarboxy-2-methylcarbonyl-16-phenoxy-17,18,19,20-tetranor-PGD₁, a prostaglandin analog according to claim
 19. 21. A prostaglandin analog according to claim 16, wherein R₇ is --(CH₂)_(m) --CH₃ --.
 22. A prostaglandin analog according to claim 21, wherein Z₁ is cis--CH--CH--CH₂ --(CH₂)_(g) --CF₂ --.
 23. 2-Decarboxy-2-methylcarbonyl-2,2-difluoro-PGD₁, a prostaglandin analog according to claim
 22. 24. A prostaglandin analog according to claim 21, wherein Z₁ is cis--CH₂ ═CH--CH--(CH₂)_(g) --CH₂ --.
 25. 2-Decarboxy-2-methylcarbonyl-cis-4,5-didehydro-16,16-dimethyl-PGD₁, a prostaglandin analog according to claim
 24. 26. A prostaglandin analog according to claim 21, wherein Z₁ is --(CH₂)₃ --(CH₂)_(g) --CH₂ --.
 27. 2-Decarboxy-2-methylcarbonyl-PGD₁, a prostaglandin analog according to claim
 26. 28. A prostaglandin analog according to claim 21, wherein Z₁ is --(CH₂ (₃ --(CH₂)_(g) --CF₂ --.
 29. 2-Decarboxy-2-methylcarbonyl-2,2-difluoro-PGD₁, a prostaglandin analog according to claim
 28. 30. A prostaglandin analog according to claim 21, wherein Z₁ is --CH₂ --O--CH₂ --(CH₂)_(g) --CH₂ --.
 31. 2-Decarboxy-2-methylcarbonyl-5-oxa-PGD₁, a prostaglandin analog according to claim
 30. 32. A prostaglandin analog according to claim 21, wherein Z₁ is --(CH₂)₂ --O--(CH₂)_(g) --CH₂ --.
 33. 2-Decarboxy-2-methylcarbonyl-4-oxa-PGD₁, a prostaglandin analog according to claim
 32. 34. A prostaglandin analog according to claim 21, wherein Z₁ is --(CH₂)₃ --O--(CH₂)_(g) --.
 35. 2-Decarboxy-2-methylcarbonyl-3-oxa-PGD₁, a prostaglandin analog according to claim
 34. 36. A prostaglandin analog according to claim 21, wherein Z₁ is --C.tbd.C--CH₂ --(CH₂)_(g) --CH₂ --.
 37. 2-Decarboxy-2-methylcarbonyl-5,6-didehydro-PGD₁, a prostaglandin analog according to claim
 36. 38. A prostaglandin analog according to claim 21, wherein Z₁ is --CH₂ --C.tbd.C--(CH₂)_(g) --CH₂ --.
 39. 2-Decarboxy-2-methylcarbonyl-4,4,5,5-tetradehydro-PGD₁, a prostaglandin analog according to claim
 38. 40. A prostaglandin analog according to claim 21, wherein Z₁ is trans--(CH₂)₂ --(CH₂)_(g) --CH═CH--.
 41. 2-Decarboxy-2-methylcarbonyl-trans-2,3-didehydro-PGD₁, a prostaglandin analog according to claim
 40. 42. A prostaglandin analog according to claim 21, wherein Z₁ is cis--CH═CH--CH₂ --(CH₂)_(g) --CH₂ --.
 43. A prostaglandin analog according to claim 42, wherein R₅ is methyl.
 44. 2-Decarboxy-2-methylcarbonyl-15-methyl-PGD₁, a prostaglandin analog according to claim
 42. 45. A prostaglandin analog according to claim 42, wherein R₅ is hydrogen.
 46. A prostaglandin analog according to claim 45, wherein one of R₃ and R₄ is fluoro.
 47. 2-Decarboxy-2-methylcarbonyl-16,16-difluoro-PGD₁, a prostaglandin analog according to claim
 46. 48. A prostaglandin analog according to claim 45, wherein at least one of R₃ and R₄ is methyl.
 49. 2-Decarboxy-2-methylcarbonyl- 16,16-dimethyl-PGD₁, a prostaglandin analog according to claim
 48. 50. A prostaglandin analog according to claim 45, wherein R₃ and R₄ are both hydrogen.
 51. 2-Decarboxy-2-methylcarbonyl-PGD₁, a prostaglandin analog according to claim
 50. 